Granulosa and Theca Cell Tumors of the Ovary John N

Henry Ford Hospital Medical Journal

Volume 8 | Number 3 Article 7

9-1960 Granulosa And Theca Cell Tumors Of The Ovary John N. Canton

C. Paul Hodgkinson

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Recommended Citation Canton, John N. and Hodgkinson, C. Paul (1960) "Granulosa And Theca Cell Tumors Of The Ovary," Henry Ford Hospital Medical Bulletin : Vol. 8 : No. 3 , 318-323. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol8/iss3/7

This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. For more information, please contact [email protected]. GRANULOSA AND THECA CELL TUMORS OF THE OVARY

JOHN N. CANTON, M.D.* AND C. PAUL HODGKINSON, M.D.*

Credit for the first description of granulosa cell tumor is given to von Werdt' and to Loeffler and PrieseF for thecoma. Collectively these tumors are known as feminizing mesenchymomas. More than 1100 granulosa cell and 300 theca cell tumors have been reported in the world literature. Age incidence is wide. A thecoma was removed from a woman aged 92 years and bilateral granulosa cell tumors from an infant aged 14 weeks. About 50% of granulosa cell tumors and 40% of thecomas occur before the menopause. Approximately 5% of granulosa cell tumors are seen in the pre-pubertal age group; however, thecomas are rare before the age of 30. Only 3 thecomas have been reported before the age of 10 and one of these in a patient under one year.

Classifications of ovarian tumors often list both granulosa cell and theca cell tumors as "functioning tumors", and some authors have reported between 60% and 95% as functional.^-'' However, in many instances, no "functioning" influence is present. In most cases the clinical parameter of function was estrinism; but rare cases have shown virilism. Depending on the age group, the earliest symptom may be precocious pseudo-puberty, menorrhagia, or postmenopausal bleeding. On physical examination an adnexal mass may be felt, but no statistics are available which show the percentage of these tumors to be palpable. Abnormal uterine bleeding incidental to the tumor is often associated with hyperplastic endometrium. Some authors'-' report an increased incidence of endometrial carcinoma in patients with granulosa cell tumor of the ovary. If in a patient with postmenopausal bleeding the first and second dilatation and curettage yields endometrium which is hyper plastic, a repeated episode of bleeding would suggest the need of laparotomy even in the absence of positive pelvic findings.

Recent publications'-" list the incidence of malignancy of granulosa cell tumor as 10% or more. The degree of malignancy of the tumor is difficult to predict even by histologic appearance. Each granulosa cell tumor should be considered potentially malignant and a thorough microscopic examination done. Only 10 cases of malignant thecomas are reported in the literature.

The granulosa cell tumor is usually unilateral and solid and varies in size from a few millimeters to 34 pounds. It may be cystic, hemorrhagic and variable in color. Microscopically the pattern is cylindromatous, microfollicular with Call-Exner bodies (Fig. 1) sarcomatous or undifferentiated. Grossly, thecomas appear similar to fibromas or leiomyomas. Microscopically they show fibrous and thecal elements and may require fat stains to differentiate them from the fibromas. Luteomas may be included here since Novak and others consider them lutinized granulosa-theca cell tumors and not a separate class.

Treatment depends upon the age of the patient. If in the prepubertal patient the tumor is bilateral, or unilateral and locally invasive, removal of both adnexae and uterus is indicated. If the tumor is unilateral and non-invasive a unilateral

''Division of Gynecology and Obstetrics.

318 Tumors of the Ovary

Figure 1 Granulosa cell tumor with Call-Exner bodies. oophorectomy is acceptable provided the patient is carefully and frequently followed. The patient in the menstrual age group presents a greater problem. Formerly, it was suggested that if the tumor was unilateral and non-invasive it was permissable to save the uterus and opposite ovary, depending upon the patient's desire for more children. Because of recurrence even when the tumor is non-invasive, confined to one ovary, and apparently benign conservatism based on age or child-bearing potential should not be considered, and patients in this group should have bilateral oophorectomy and hysterectomy.

In the postmenopausal patient, regardless of one or both ovary involvement, bilateral oophorectomy and hysterectomy are indicated. Radiation is best reserved for patients in whom invasion or recurrence is proved. Granulosa cell tumors

319 Canton and Hodgkinson

have been known to recur 22 years following surgery and may respond well to radiation. Treatment of thecomas is the same as for any benign unilateral ovarian lesion unless malignancy upon microscopic examination is shown. Patients with either type of tumor should be closely followed for the rest of their lives.

CASE DISCUSSION This report is of 17 patients, three of whom present unusual features. The earliest symptoms included some form of abnormal uterine bleeding in six of the ten patients with granulosa cell tumors and four of the seven with thecomas. A definite pelvic mass was present preoperatively in only seven of the 17. Total hysterectomy and bilateral salpingo-oophorectomy was performed on 11 patients and unilateral oophorectomy with or without hysterectomy on the remaining 6. Two patients received radiation, one of whom is still living.

In our granulosa cell tumor group the mortality was 30%. This figure is deceptive just as are the figures in many large series which show five-year cure rates but fail to allow for late recurrence of the tumor. A summary of granulosa and theca cell tumor cases seen at this clinic for the past 30 years is shown in Table I.

Case No. 13 represents one of the youngest patients with thecoma yet reported. In 1950 no case of thecoma in a patient under age 16 had been reported, but by 1959 there were 5, one of whom was less than one year old. Our patient was 13 years of age, and onset of menses was at age 10. The menses were regular until age 11 'A when the patient because of excessive bleeding was examined by a physician. The patient was given "shots and pills" to control the menses but with only partial success. The patient was first seen at this hospital because of excessive bleeding, and the significant findings were development of secondary sex character istics beyond that expected for her age and an adnexal mass considered to be a granulosa cell tumor preoperatively. At operation a thecoma was found, and fat stains were done to differentiate it from a "cellular fibroma". The patient is reported without recurrence IV2 years after unilateral oophorectomy.

Case No. 2 is unusual because the patient had a recurrence of tumor in her remaining ovary 18 years after the original tumor was removed and one year later died of widespread metastases. Case No. 9 represents a patient who had had a unilateral oophorectomy for a granulosa cell tumor, and eight years later developed recurrence in the other ovary. This ovary, and a granulosa cell tumor mass on the serosa of the colon were excised, and a biopsy of an infiltrating lesion of the pelvic wall which also proved to be granulosa cell was done. The patient received 2,400 r of deep x-ray therapy and is living without further evidence of recurrence after five years.

DISCUSSION The experience at this clinic with granulosa and theca cell tumors of the ovary is similar to that reported in the literature. The number of "functional" tumors found and the percentage of tumors clinically palpable are less than other authors

320 Table I YEARS PRESENTING SIGNS HORMONE TREATMENT PATHOLOGY FOLLOW-UP CASE AND SYMPTOMS ACTIVITY SURVIVED 1. S. B. Symptoms & signs of P.I.D.— None Hyst. Bilat. S&O. Micro, focus No data. Presented for age 33 chronic. Granulosa cell tumor statistical reasons only. 2. C. H. Unknown. Unknown Hyst. Bilat. S&O. Granulosa Died 18 years after pri 18 age 51 Recurrent 16 yrs. later mary due to wide met to pelvis & colon. astases. 3. M. K. Postmenopausal bleeding 1 yr. Yes Hyst. Bilat. S&O. Granulosa cell tumor. Living and well in 1959, 6 plus age 53 D&C endo. hyperplasia. Estrin no recurrence. alive 4. E. R. Menorrhagia for 3 mos. Irreg. Yes Hyst. & Unilat. S&O. Granulosa cell tumor. 7 yrs. postop. carcino 8 age 43 menses 2 yrs. Estrin matosis with Ca. R. ovary as primiary. 5. R. A. Postmenopausal bleeding I wk. & Yes Hyst. Bilat. S&O. Granulosa cell tumor. Living and well in 1959, 7 plus age 61 L. adnexal mass. Estrin 2800 r of X-ray no recurrence. alive 6. E. R. Postmenopausal bleeding 8 mos. Yes Hyst. Bilat. S&O. Granulosa cell tumor. Living and well in 1959, 11 plus age 62 No adnexal mass. D&C—endo. Estrin no recurrence. alive hyperplasia, bled after D&C. 7. T. L. Menomelrorrhagia for 10 mos. No Yes Unilat. oophorectomy Granulosa cell tumor. Had 3 full-term preg. 8 plus age 32 adnexal mass. Uterus 5 mos. preg. Estrin and appendectomy. with normal infants. L alive gestation size. &W, no recurrence. 8. E. R. Bilat. oophorectomy, because met 7 Bilat. Oophorectomy. Granulosa cell tumor. 1 yr. postop. no recur I plus age 48 astatic Ca of breast. Estrin rence. alive 9r"M. K. Oligomenorrhea for 3 yrs. Profuse Yes Hyst. & Unilat. S&O—1946. Granulosa cell tumor L. ovary, Had 2400 r Radiation 13 plus age 39 bleeding 2 wks. p.t.a. after menses Estrin Other ovary removed 8 yrs, Recurrent granulosa cell tumor following 2nd surgery. alive irreg. 3 mos. later due asympt. R. ovary, colon, and pelvic wall. No evidence of recur pelvic mass. rence 5 yrs. after radi ation. 10. V. A. Asymptomatic adnexal mass. None Hyst. Bilat. S&O. Thecoma benign Too recently done. age 52 Ti7~M.Tr Postmenopausal bleeding for 2 Yes Total hyst. Bilat. S&O. Thecoma benign Unknown. age 54 mos. No adnexal mass. Estrin l2r"R.T^ Postmenopausal bleeding 5 mos. Yes Bilat. S&O, HYST, Thecoma with Unknown. age 63 D&C. endo. hyperplasia, no mass. Estrin some granulosa cells 13. C. T. Menarche age 10 yrs. Irreg. & pro Yes Unilat. S&O. Thecoma, benign No recurrence with reg. 7 plus age 13 fuse at ll'A. Adnexal mass felt. Estrin menses 7 plus years. alive 14. A. G. Abdominal mass. No bleeding. Im None Unilat. oophorectomy. Thecoma, benign No recurrence. 15 plus age 62 pression; fibroid or ovarian tumor. alive 15. M. M. Menorrhagia 1 yr. Impression: Yes Hyst. and R. oophorectomy. Thecoma, benign Unknown. age 47 fibroid. Estrin 16. V. A. Stress incontinence, no vag. bleed 9 Total hyst. R. oophorectomy. Combination of thecal & No recurrence. 3 plus age 62 ing. R. Ovarian cyst. Left previously. granulosa cell without definity. alive 17. C. G. Pelvic & back pain for 8 mos. L. None Hyst. Bilat. S&O., CO" Anaplastic granulosa cell ca, Died in four monthsj Died in age 62 flank & lower abdominal pain for (6800 r) not encapsulated—tube removed. due to metastases. four mos. 2 mos. Canton and Hodgkinson report. The mortality rate compares with similar series and is high enough to consider all granulosa-cell tumors as potentially malignant.

The results of unilateral versus bilateral oophorectomy with or without hysterec tomy, as related to prognosis, is not as clear-cut in this series as it is in others. However, bilateral surgery does appear to offer the best chance for survival. Several cases reported elsewhere show unilateral, non-invasive and well-differentiated granulosa cell tumors to have been found in patients 18-30 years of age. These patients were treated by conservation of one ovary and later developed fatal recurrences. The gynecologist who finds a granulosa cell tumor in a patient in the menstrual age group must carefully consider further treatment indicated on the basis of all available information. There is no clear-cut basis for the management of these patients, and each must be given individual consideration. Some gynecologists consider the patient's desire for future child-bearing as a basis for conservative management while others feel that malignant or potentially malignant tumors should be treated the same in all patients regardless of age.

SUMMARY

This report is a survey of 17 cases of granulosa cell and theca cell tumors and represents a 30-year experience at this clinic. Three cases show unusual features. Age is the chief factor considered in treatment. The mortality rate, number of functional tumors found and surgical treatment are compared with similar series appearing in the literature.

REFERENCES

1. von Werdt, P.: Ueber die Granulosazelltumoren des Ovariums, Beitr. z. path. Anat. 59:453, 1914. 2. Loffler, E., and Priesel, A.: Bindegewebige Gewache des Eierstockes von besonderer Bauart (Fibroma thecocellulare xanthomatodes ovarii) Beitv. z. path. Anat. u. z. AUg. Path. 90:199, 1932. 3. Bland, P. B., and Goldstein, L.: Granulosa cell and brenner tumors of the ovary; report of case with review of those cases already recorded, Surg., Gynec. & Obst. 61:250, 1935, 4. Varangot, J.: Les tumeurs de la granulosa, Paris, Librairie Louis Arnette, 1937. 5. Dockerty, M. A., and MacCarty, W. C: Granulosa cell tumors, with the report of a thirty-four pound specimen and a review, Am. J. Obst. & Gynec. 37:425, 1939. 6. Mansell, H., and Hertig, A. T.: Granulosa-theca cell tumors and endometrial carcinoma, a study of their relationship and a survey of 80 cases, Obst. & Gynec. 6:385, 1955. 7. Novak, E.: Gynecologic and Obstetric Pathology, ed. 4, Philadelphia, Saunders, 1958. 8. Morris, J. M., and Scully, R. E.: Endocrine Pathology of the Ovary, St, Louis, Mosby, 1958.

. ADDITIONAL REFERENCES

Anderson, W. A. D.: Pathology, ed. 3, St. Louis, Mosby, 1957, p. 1076. Barter, R. H., and Parks, J.: Current concepts of ovarian surgery, Obst. & Gynec. 7:62, 1956. Busby, T., and Anderson, G. W.: Feminizing mesenchymomas of the ovary, includes 107 cases of granulosa, granulosa-theca-cell and theca-cell tumors. Am. J. Obst. & Gynec. 68:1391, 1954. Diddle, A. W.: Granulosa and theca-cell ovarian tumors: prognosis. Cancer 5:215, 1952.

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Diddle, A. W., and Devereux, W. P.: Ovarian mesenchymomas: A five-year follow-up study, Obst. & Gynec. 13:294, 1959. Gordon, V. H., and Marvin, H. N.: Theca-ceU tumor of ovary in child one year of age, with review of the literature, J. Pediat. 39:133, 1951. Jones, G. E. S., and TeLinde, R. W.: The curability of granulosa-cell tumors. Am. J. Obst. & Gynec. 50:691, 1945. Knight, W. R.: Theca-cell tumors of the ovary with a report of 15 cases and a review of the literature. Am. J. Obst. & Gynec. 56:311, 1948. Lewis, T. L. T.: Progress in Clinical Obstetrics and Gynecology, Boston, Little, Brown, 1956, p.574. Pedowitz, P., Felmus, L. B., and Mackles, A.: Precocious pseudopuberty due to ovarian tumors, Obst. & Gynec. Surv. 10:633, 1955. Rubin, I. C, and Novak, J.: Integrated Gynecology, New York, McGraw-Hfll, 1956, v.2, p.46. Sternberg, W. H., and Gaskifl, C. J.: Theca-cell tumors. Am. J. Obst. & Gynec. 59:575, 1950. TeLinde, R. W.: Granulosa-cell tumors of the ovary and their relation to postmenopausal bleeding, Am. J. Obst. & Gynec. 20:552, 1930. Tweeddale, D. N., Dockerty, M. B., Pratt, J. H., and Hranilovich, G. T.: Pregnancy with a recurrent granulosa-cell tumor. Am. J. Obst. & Gynec. 70:1039, 1955. Tweedie, F, J.: Precocious pseudopuberty of ovarian origin with report of two cases, Am. J. Obst. & Gynec. 75:964, 1958. Ullery, J. C, and Boutselis, J. G.: The gross pathology, diagnosis and clinical management of ovarian enlargements, Obst. & Gynec. Surv. 14:635. 1959. Wilkins, L.: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adoles cence, Springfield, Thomas, 1950, p.156.

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